Preventive effects of betulinic acid on streptozotocinnicotinamide induced diabetic nephropathy in male mouse

Ahangarpour, Akram; Oroojan, Ali Akbar; Khorsandi, Layasadat; Shabani, Razieh; Mojaddami, Shahnaz

doi:10.15171/jnp.2016.24

Cited by 25 publications

(14 citation statements)

References 22 publications

(24 reference statements)

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“…Seven days after the injections, blood glucose levels were evaluated. Mice with blood glucose more than 200 mg/dL were used in the following experiments ( 11 ).…”

Section: Methodsmentioning

confidence: 99%

“…BA has been extracted from various plants including Morus Alba root bark ( 8 ), Bersama engleriana ( 9 ), Quisqualis fructus , Coussarea paniculata , Caesalpinia paraguariensis , Vitex negundo , Berlinia grandiflora , Ziziphus joazeiro , Uapaca nitida , Ipomea pes-caprae , Ancistrocladus heyneanus , Diospyros leucomelas , and Syzygium claviforum ( 10 ). BA protects liver through antioxidant and anti-inflammatory activities ( 11 ). Interestingly BA and some of the aforementioned plants are effective in the treatment of type 2 diabetes ( 12 13 )…”

Section: Introductionmentioning

confidence: 99%

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The effect of betulinic acid on leptin, adiponectin, hepatic enzyme levels and lipid profiles in streptozotocin-nicotinamide-induced diabetic mice

Ahangarpour¹,

Shabani²,

Farbood³

2018

Res Pharma Sci

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Diabetes mellitus is developed by lack of insulin secretion or reduction of tissues sensitivity to insulin, which lead to serious complications. The aim of this study is to evaluate antihyperlipidemic effect of betulinic acid (BA) on streptozotocin-nicotinamide (STZ-NA) induced diabetic mice. In this experimental study, seventy adult male NMRI mice (20-25 g) were divided randomly into seven groups (n = 10) of control, sham, diabetes, diabetes + BA (10, 20 and 40 mg/kg), and diabetes + metformin (200 mg/kg). Diabetes was induced by intraperitoneal (i.p.) injection of a single dose of STZ (50 mg/kg) 15 min after an i.p. administration of nicotinamide (NA) (120 mg/kg). BA and metformin were orally administered and after two weeks blood samples were taken. Blood levels of leptin, adiponectin, lipid profile and liver enzyme were then measured. One day after the last drug administration, liver was removed to evaluate the histological changes. A significant increase (P < 0.05) in the plasma levels of leptin, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), alkaline phosphatase (ALP), low density lipoprotein cholesterol (LDL-C), cholesterol, and a significant decrease in adiponectin and high density lipoprotein cholesterol (HDL-C) were observed in diabetic mice. The groups treated with BA indicated a significant decrease in leptin, AST, ALT, ALP, TG, cholesterol, LDL-C and an increases in adiponectin and HDL levels, while VLDL did not show significant changes. BA was found to have positive effects on liver injury. BA has an effective role on liver damage induced by diabetes through amelioration of leptin, adiponectin, liver enzyme levels and lipid profile. Since BA has a positive effect on lipid profile, adiponectin and leptin, it may improve metabolic syndrome.

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“…Seven days after the injections, blood glucose levels were evaluated. Mice with blood glucose more than 200 mg/dL were used in the following experiments ( 11 ).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effect of betulinic acid on leptin, adiponectin, hepatic enzyme levels and lipid profiles in streptozotocin-nicotinamide-induced diabetic mice

Ahangarpour¹,

Shabani²,

Farbood³

2018

Res Pharma Sci

Self Cite

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“…daily for 2 weeks), Type 2 diabetic as negative control (received STZ 50 mg/kg in 0.1 mL citrate buffer pH 4.5, 15 min after a single dose of NA 120 mg/kg in 0.1 mL normal saline, i.p. ), Type 2 diabetic + BA, received 10, 20 and 40 mg/ kg, in 0.3 mL normal saline (Xie et al, 2017) daily gavage for 2 weeks after induction of type 2 diabetes, and Type 2 diabetic + metformin as positive control, received 200 mg/ kg in 0.3 mL normal saline, daily gavage for 2 weeks after induction of type 2 diabetes (Ahangarpour et al, 2016b).…”

Section: Experimental Designmentioning

confidence: 99%

“…An in vitro incubation of BA in human aortic smooth muscle cell (HASMC) showed that BA can decrease the intracellular reactive oxygen species (ROS), and suppress the nuclear translocation and phosphorylation of IRB-α under high glucose conditions; therefore, BA can inhibit diabetic vascular disease (Yoon et al, 2010). BA has a preventive effect on diabetic nephropathy during diabetic situations (Ahangarpour et al, 2016b). In contrast, administration of BA in STZ-NA diabetic treated mice can induce a worse outcome in the male reproductive system (Ahangarpour et al, 2016c).…”

Section: Introductionmentioning

confidence: 99%

Anti-diabetic effect of betulinic acid on streptozotocin-nicotinamide induced diabetic male mouse model

Birgani

Ahangarpour

Khorsandi

et al. 2018

Braz. J. Pharm. Sci.

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Diabetes is a metabolic disease caused by abnormal insulin secretion or action. In the present study, the effects of betulinic acid (BA, a triterpene) are evaluated on glucose, α-amylase and plasma insulin levels, insulin resistance and the histopathology of pancreatic islets in streptozotocin-nicotinamide (STZ-NA) diabetic mice. Seventy adult male NMRI mice were randomly divided into seven groups: control, sham, diabetic, diabetic treated with BA (10, 20 and 40 mg/kg) and diabetic treated with metformin (200 mg/kg). Diabetes was induced in mice by intraperitoneal injection of streptozotocin 50 mg/kg after a dose of nicotinamide 120 mg/kg. Two weeks after treatment with BA, blood samples were collected for measuring glucose, α-amylase and insulin levels, and the pancreas was isolated for histopathology evaluation. Diabetes reduced the number and diameter of pancreatic islets, and increased α-amylase and insulin resistance. BA treatment reduced blood glucose, α-amylase and improved insulin sensitivity as well as pancreas histopathology. In addition, BA showed stronger effects on the pancreatic histology and insulin resistance compared to the metformin group.

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“…For example, betulinic acid has been reported to possess anti-cancer, anti-viral, anti-HIV, anti-inflammatory, anti-leukemic, anti-diabetic, anti-hyperlipidemic, anti-bacterial, and anti-mycobacterial activities [5; 25; 26; 38; 41; 71; 86; 87; 94]. Betulinic acid has also been shown to be effective in reducing effects of metabolic syndrome and preventative in diabetic nephropathy [1; 65]. It was reportedly protective against ischemic complications as well as a potential therapy for Alzheimer’s disease, atherosclerosis and other vascular diseases [35; 36; 59].…”

Section: Discussionmentioning

confidence: 99%

Betulinic acid, derived from the desert lavender Hyptis emoryi, attenuates paclitaxel-, HIV-, and nerve injury–associated peripheral sensory neuropathy via block of N- and T-type calcium channels

Bellampalli

Moutal

et al. 2018

Pain

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The Federal Pain Research Strategy recommended development of nonopioid analgesics as a top priority in its strategic plan to address the significant public health crisis and individual burden of chronic pain faced by >100 million Americans. Motivated by this challenge, a natural product extracts library was screened and identified a plant extract that targets activity of voltage-gated calcium channels. This profile is of interest as a potential treatment for neuropathic pain. The active extract derived from the desert lavender plant native to southwestern United States, when subjected to bioassay-guided fractionation, afforded 3 compounds identified as pentacyclic triterpenoids, betulinic acid (BA), oleanolic acid, and ursolic acid. Betulinic acid inhibited depolarization-evoked calcium influx in dorsal root ganglion (DRG) neurons predominantly through targeting low-voltage-gated (Cav3 or T-type) and CaV2.2 (N-type) calcium channels. Voltage-clamp electrophysiology experiments revealed a reduction of Ca, but not Na, currents in sensory neurons after BA exposure. Betulinic acid inhibited spontaneous excitatory postsynaptic currents and depolarization-evoked release of calcitonin gene-related peptide from lumbar spinal cord slices. Notably, BA did not engage human mu, delta, or kappa opioid receptors. Intrathecal administration of BA reversed mechanical allodynia in rat models of chemotherapy-induced peripheral neuropathy and HIV-associated peripheral sensory neuropathy as well as a mouse model of partial sciatic nerve ligation without effects on locomotion. The broad-spectrum biological and medicinal properties reported, including anti-HIV and anticancer activities of BA and its derivatives, position this plant-derived small molecule natural product as a potential nonopioid therapy for management of chronic pain.

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Preventive effects of betulinic acid on streptozotocinnicotinamide induced diabetic nephropathy in male mouse

Cited by 25 publications

References 22 publications

The effect of betulinic acid on leptin, adiponectin, hepatic enzyme levels and lipid profiles in streptozotocin-nicotinamide-induced diabetic mice

The effect of betulinic acid on leptin, adiponectin, hepatic enzyme levels and lipid profiles in streptozotocin-nicotinamide-induced diabetic mice

Anti-diabetic effect of betulinic acid on streptozotocin-nicotinamide induced diabetic male mouse model

Betulinic acid, derived from the desert lavender Hyptis emoryi, attenuates paclitaxel-, HIV-, and nerve injury–associated peripheral sensory neuropathy via block of N- and T-type calcium channels

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